Ochratoxin A and B are produced as secondary metabolites by certain strains of A. ochraceus, and are known to produce diseases in livestock. The objective of the proposal is to define the mechanism for the effects of ochratoxin A at cellular and subcellular levels. The data obtained may lead to a better concept of the pathology of ochratoxin A, as well as structurally related secondary metabolities produced by microorganisms. By using radioactively labelled ochratoxin A, I hope to examine the relationship between uncoupler-dependent uptake of the toxin and the inhibition of exchange diffusion carriers in mitochondria. Ascites tumor cells will be used to measure the effects of ochratoxin A on glycolysis, respiration, and cellular transport systems. The metabolism of ochratoxin A will be studied in an in vitro microsomal system, using tissues of different species from ducklings to monkeys. The information gathered will be used to construct a biochemical model for the mechanism of action of ochratoxin A.